The proposed research is designed to examine brain monoamines, neuroendocrine interactions, and related behaviors in offspring of animals injected with phenobarbital during stages of gestation when these systems are beginning to function. Emphasis will be placed on long-term alterations in these systems but transient changes as they contribute to long-term changes will also be examined. Potential changes in monoamine neurotransmitter function will be assessed by determination of levels, synthesis, turnover and uptake of monoamines, and activities of their key regulatory enzymes. Changes in neuroendocrine interactions will be assessed by examination of plasma corticosterone in stressed and non-stressed animals, by measurement of corticosterone in neonatal adrenals, and by assay of FSH, LH, testosterone, estradiol and progesterone in animals prenatally exposed to phenobarbital. Behavioral studies will emphasize an assessment of reactivity to stimulation, performance of discrimination problems in mature offspring. These studies will be designed to allow potential correlation of results of subsequent monoamine and endocrine assays on the same animals. Developmental studies will be included to assess the contribution of early developmental changes to long term dysfunctions. BIBLIOGRAPHIC REFERENCES: Middaugh, L.D., Santos, C.A. and Zemp, J.W. Phenobarbital during Pregnancy Alters Operant Behavior of Offspring in C57B1/6J Mice. Pharmacol. Physiol. & Behav. 3:1137-1139 (1975). Zemp, J.W. and Middaugh, L.D. Some Effects of Prenatal Exposure to the Amphetamine Sulfate on Developmental Neurochemistry and on Behavior. Int. J. Addict. Dis. 2:207-331 (1975).